Precise Genome Engineering Center, School of Life Sciences, Guangzhou University, Guangzhou 510006, China.
Precise Genome Engineering Center, School of Life Sciences, Guangzhou University, Guangzhou 510006, China.
Mitochondrion. 2021 Jul;59:37-47. doi: 10.1016/j.mito.2021.04.007. Epub 2021 Apr 17.
Alzheimer's disease (AD) is an age-dependent, incurable mental illness that is associated with the accumulation of aggregates of amyloid-beta (Aβ) and hyperphosphorylated tau fragments (p-tau). Detailed studies on postmortem AD brains, cell lines, and mouse models of AD have shown that numerous cellular alterations, including mitochondrial deficits, synaptic disruption and glial/astrocytic activation, are involved in the disease process. Mitophagy is a cellular process by which damaged/weakened mitochondria are selectively eliminated from the cell. In AD, impairments in mitophagy trigger the gradual accumulation of defective mitochondria. This review will focus on the recent progress in understanding the molecular mechanisms and pathological role of mitophagy and its implications for AD pathogenesis. We will also discuss the novel concept of the regulation of mitophagy as a therapeutic avenue for the prevention and treatment of AD.
阿尔茨海默病（AD）是一种与β淀粉样蛋白（Aβ）聚集物和过度磷酸化的 tau 片段（p-tau）积累相关的、年龄依赖性的、不可治愈的精神疾病。对 AD 患者死后大脑、细胞系和 AD 小鼠模型的详细研究表明，许多细胞变化，包括线粒体缺陷、突触破坏和神经胶质/星形胶质细胞激活，都与疾病过程有关。自噬是一种细胞过程，通过该过程，受损/弱化的线粒体从细胞中被选择性地清除。在 AD 中，自噬的损伤会触发缺陷线粒体的逐渐积累。这篇综述将重点介绍对自噬分子机制和病理作用的理解方面的最新进展，及其对 AD 发病机制的影响。我们还将讨论自噬调节作为 AD 预防和治疗的治疗途径的新概念。
